PP: Antoncho said that performing the reaction in MeOH would directly methoxylate the quinone to the 2-alkyl-dimethoxyhydroquinone, so when it's time for the amination, the molecule should already be aromatic. But you are right, if there would be quinone carbonyls left, they would also aminate.

It woulde be wonderful if it could be done in one pot, but I really suspect that purification is required at least somewhere along the way.

Yes, I agree completely, it would have to be done, sadly. I was referring to the insanely beautiful idea of halfapint's: To alkylate the quinone with 3-oxobutanoic acid to form the propanone/qionone, then reductively aminate and reductively alkylate the molecule in one step with Al/Hg/MeNO2/MeOH where the MeOH is the solvent alcohol, source for the Al/Hg reduction for the propanone, and also the fuel for the reductive alkylation of the qionones in one pot. Ingenious idea, but possibly problematic.

                                                   PrimoPyro

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Vivent Longtemps la Ruche!

Boy wuz i wrong!!! n-Methyl what Sorry, beez.

Anywayz:
 like i didn't say, if you wanted to reduce 2,5-dioxo-phenylpropan-2-one to the amine by first producing say the oxime... hmm. Can't be done. Wait a minute.

? About bisulfites: does benzoquinone precipitate a bisulfite addition product?

? Next: Requires more vigorous conditions to methylate benzoquinone reductively with methanol than to reductively aminate *-propanone with say benzylamine you could hydrolyze off..?

? Also: I'm lost here, beez, so if you could sorta help me out I'd bee mighty appreciative...

OK, looks like the only way out is to reduce the methanol solution, before it gets any nitrogen in the pot. With any luck the quinone's redox threshold potential, whatever it's called, is lower than that of *-isopraponone. Won't fructose reduce benzoquinone? Time to use more silver?

Oh, well, you have to lose the carbonyl to reduction, too, most probably. Then you have to take the 2,5-dimethoxyphenyl propan-2-ol, and reoxidize it back to the *-propan-2-one, so then you can re-reduce it to the amine.

Was even wanting to try the Leukart-Wallach on this one, afraid I'd end up with some kind of aniline stuff...

Oh, all that splendid simplicity, down the tubes... IMPossible.

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a half a pints a half a pound a half a world a half a round
demimonde, n. Half world.

Like to see that at least one of my post is not only replied  by rhodium only! I'm totally with rhod when he says that some investissement in new roads to new or old compounds is required. It is only with research from all the hive that we are advancing in our quest, shulgin has done very good work,  I consider himself as one of the best genius in our population, but he become more or less old and some investisment from the youth must be done. We have a big advantage on him: we are several chemists and various peoples connected by internet between us, but he was more or less alone. If we join our forces in Research and Development like any competitive enterprise should do, we could change the face of the world, and the psychedelic renewal may take place. I will be very happy if all this theoretical discussion become a practical one, with some bees puting time, money and personal failure/success for the  community. So get up, stand up and fight the war!!

Love you all, P iX

Halfapint: Benzoquinone forms bisulfite adducts yes, and catalytic hydrogenation of N-benzyl-MDA will give toluene and MDA.

we are several chemists and various peoples connected by internet between us, but he was more or less alone. If we join our forces in Research and Development like any competitive enterprise should do, we could change the face of the world, and the psychedelic renewal may take place.

Yes, think of us as a 2500 node neural network all running 486-processors - in some instances we do approach the ingenuity of Shulgin. Give the board a few more years, and this place really should have its own quarterly journal: "Journal of Clandestine Chemistry" published free on the web with the latest advances of the area featured in it, with PDF downloads and all, and in 2012 we will attain University status, and be able to issue diplomas in different clandestine chemistry interest areas.  

>4-MAR

What the hell is 4-MAR?

4-methylaminorex. See the novel discourse thread by Rhodium called "4-MAR without CNBr" and the standard syntheses on his website.

Also known as U4Euh, and ice.

                                                     PrimoPyro

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Vivent Longtemps la Ruche!

halfpint - i wasted alot of time trying to use bisulfite to purify post benzo wackers, i finally gave up because of all the benzoquinone (or what i thought was) that carried over using that method. i never triied react the benzoquinone directly with bisulfite sol. to test but the impression i got was that it did.

Rhodium, the quarterly is an awesomely beautiful idea!!!

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7.10.01

some research at library:

reductive methylation of quinone are usualy done with CH3I or DMS or DMC. This ref (synth comm 16(9), 137-42 (1986)) say that with DMS and Na2S2O8 ketone are not reduced, but quinone are. No propan-2-ol in these condition.
Two other ref may be useful: Zh.Obshch. khim (1982), 52(12), 2778-80 tell us about polarographic(? what's this) reduction of quinone in basic MeOH lead to 4-methoxy phenol. A mixture of product may emerge with our compound, and an alkylation step is required, but maybe tweetio may be doable. This last ref is the better I think: Gazz. chim. ital (1943) 73 300-305 say that quinone in 80%MeOH with AL/Hg lead to 1,4 dimethoxy benzene. Some italian bee in the hive?

Two other things:
1) I don't know if this reaction will work with acetoacetic acid because I haven't see any oxo acid used in the refs. I fear that the reaction will cleave the ketone, but I don't think so.
2) I hope that the reaction will not cleave the amides because I'm thinking of this method of protection for the amine of the 3-amino-butyric acid (with acetyl chloride for instance). Then maybe reduct the amide to the amine with Al/Hg or Zn. Or what other protection could we use?

PrimoPyro: I like your idea with succinimide, hope it work

Polarography is some kind of electroreduction. We have italians among us (Peyote for example), so if you post the article, he could translate it. The acetoacetate used in the reaction could easily be protected as the ethylene glycol acetal (to form the 1,3-dioxolane) with antifreeze and H2SO4, and then reacted with the quinone.

Reductive-alkylation and aromatic coupling reactions of 1,4-benzoquinone derivatives promoted by ethylaluminum dichloride.
Ferreira, Vitor F.; Schmitz, Francis J.   
J. Organomet. Chem.  (1998),  571(1),  1-6.

4-Ethoxyphenol
Obtained in 77% yield from 1,4-benzoquinone (120 mg, 1.10 mmol); m.p. 65-66 (lit. 65-67°C);
 
General procedure
To a solution of the appropriate benzoquinone derivative (1 mmol) in 5 ml of dry dichloromethane, 2 ml (two equivalents) of a solution of 1 M EtAlCl2 in hexane was added dropwise under a nitrogen atmosphere over a period of 30 min at -78°C. The solution turned deep blue and was stirred at this temperature for 1 h and then for 2 h at room temperature. To this mixture, 2 ml of methanol, 10 ml of water and then 5 ml of 15% HCl (to pH ~6) were slowly added sequentially. The resulting gelatinous mixture was extracted with dichloromethane (3×15 ml). The resulting cloudy, organic phase was filtered through a celite column, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residues were chromatographed on silica gel columns or preparative TLC plates and eluted with a mixture of hexane:ethyl acetate (9:1).


On the 1,6-addition of alkylamuninium compounds to para-quinones
Z. Florjanczyk and E. Szymanska-Zachara.
J. Organomet. Chem. 259 (1983), p. 127

Procedure
The reactions were carried out under nitrogen in a vessel equipped with a stirrer and connected through a liquid seal to a burette. A toluene solution of quinone was prepared in the vessel, and a toluene solution of an organoaluminium compound or a nitromethane solution of AlCl, was then introduced with vigorous stirring. When reaction was complete, the mixture was treated with water or 1 M HCl and the organic and aqueous layers were separated. Both layers were concentrated and the products isolated from them as indicated below.  4-Ethoxyphenol was extracted with petroleum ether.
Mol ratio: quinone/organoaluminium compound = 1, solvent: toluene, 500 cm3, quinone concentration 0.07 mol 1-l; temp. -78C; time 2 h.

1,4-Benzoquinone with MeAlCl2,
Yeild 54% hydroquinone, 0% 4-Methoxyphenol

1,4-Benzoquinone with EtAlCl2,
Yeild 29% hydroquinone, 20% 4-Ethoxyphenol

1,4-Benzoquinone with Et3Al
Yeild 59% hydroquinone, 8% 4-Ethoxyphenol


Reactions of organoaluminium compounds with benzoquinone
J. Organomet. Chem. 112 (1976), p. 21
Note: Similar to above done in toluene, the yeilds suck.


Preparative electrochemical reductive methylation of ortho-hydroxy-para-benzoquinones
Tetrahedron  (1997),  53(2),  469-478.
Abstract
An electrochem. methodol. for the protection of the ortho-hydroxy-para-benzoquinone functionality has been developed, by a one step formation of the arom. ethers of the reduced quinone function, improving the yields obtained for this reaction by the classical chem. methods.
 

Reductive methylation of quinones.    
Gripenberg, Jarl; Hase, Tapio.       
Acta Chem. Scand.  (1963),  17(,  2250-2. 
Journal  written in English.  
Abstract
Quinones with high oxidn.-redn. potentials were reductively methylated with Me2SO4 in the presence of C5H5N.  Thus, 0.8 ml. Me2SO4, 5 ml. MeOH, and 0.23 ml. C5H5N refluxed 1 hr., the soln. chilled and treated with 0.3 g. p-benzoquinone (I) in 5 ml. MeOH, and the cooled (ice-salt bath) mixt. basified with 5 g. NaOH in 10 ml. MeOH and steam distd. 5 min. later gave 285 mg. 1,4-(MeO)2C6H4.  Similarly, toluquinone gave 60% 2,5-(MeO)2C6H3Me, and p-mentha-3,6-diene-2,5-dione (redn. time 2 hrs.) afforded 30% 2,5-dimethoxy-p-cymene.  The procedure was modified for less reactive quinones as follows: 0.3 g. 2,5-diphenylbenzoquinone, 5 g. K2CO3, 0.1 ml. C5H5N, 0.33 ml. Me2SO4, and 10 ml. MeOH refluxed 8 hrs. gave 265 mg. 2',5'-dimethoxy-p-terphenyl, m. 154°.  Likewise, 1,2- and 1,4-naphthoquinone gave 10% 1,2 and 14% 1,4-dimethoxynaphthalene, resp.  From reductive methylations with tetramethylbenzoquinone, 2,5-dimethoxybenzoquinone (IV), 7-isopropyl-1-methylphenanthrenequinone, and anthraquinone only unchanged quinones were recovered, while 2,5-dihydroxybenzoquinone gave IV.  I added to an ice-cold soln. of 1-methylpyridinium hydroxide in H2O produced 1-methyl-2(1H)-pyridone, which indicated that quinones of high oxidn. potential could be used to oxidize alkylpyridinium hydroxides.


This might have something interesting in it

A study of an oxidative-amination method for the synthesis of aminoquinones.    
Crosby, Alan H.; Lutz, Robert E.    
J. Am. Chem. Soc.  (1956),  78  1233-5.
Abstract
Finely powd.  Cu(OAc)2.H2O (20 g.), 0.6 mole of the appropriate secondary amine, and 300 cc.  MeOH stirred, the soln. flushed with O and treated cautiously with cooling at 20-30° with 10.8 g. 1,4-benzoquinone in 200 cc. MeOH, the mixt. cooled after the O absorption ceased (30-60 min.) to 10° and filtered (if the product was sparingly sol.) or evapd. at room temp. in vacuo, the residue treated with 300 cc. Et2O and 22 cc. 96% H2SO4 and 500 cc. H2O, the aq. layer extd. with Et2O, the combined Et2O layer and ext. evapd., the residue extd. with hot iso.ovrddot.octane, and the ext. evapd. in an air stream gave the corresponding 2,5-di(substituted-amino)-1,4-quinone (substituted-amino group, phys. appearance, cor. m.p., and % yield given): Et2N (I), red needles, 112-14° (iso.ovrddot.octane-EtOH), 44; morpholino (II), red needles, 232-8° (decompn.) (from dioxane), 96 [II was also obtained by heating 2,5-dimethoxy-1.4-benzoquinone (III) in excess morpholine]; piperidino (IIIa), purple-red cubes, 179-80° (from EtOH) (decompn.), 89; Me(Me2CH)N (IV), red needles, 111-13° (from iso.ovrddot.octane-EtOH), 48; Pr2N, red clusters, 55-7° (from iso.ovrddot.octane), 45; Bu2N, red waxy solid, 45-7° (from iso.ovrddot.octane), 55; Me(PhCH2)N, red blades, 176-8° (from EtOH-dioxane) (decompn.), 86.  The appropriate quinone in a min. of Ac2O treated with several cc. dry Et3N and excess Zn dust, the mixt. warmed with stirring and filtered hot, and the filtrate cooled and poured into H2O or extd. with Et2O gave the corresponding N-substituted 2,5-diaminohydroquinone diacetates (substituted amino group, crystal form, m.p., and % yield given): Et2N, blades, 48-50° (from iso.ovrddot.octane), 40; morpholino, -, 242-3° (from EtAc-Me3COH), 58; piperidino, tabular, 166-7° (from EtOAc), 90; Me(Me2CH)N, plates, 117-19° (from iso.ovrddot.octane-EtOAc), 77; Pr2N, plates, 71-2° (from iso.ovrddot.octane), 35; Bu2N, clusters, 50-1° (from iso.ovrddot.octane), 32; Me(Ph CH2)N, prisms, 153-5° (from dioxane-EtOAc), 80. 2,5-Diethoxy-1,4-benzoquinone (V) (1.0 g.) and 4.0 g. iso-Pr2NH(VI) in 100 cc. Me3COH refluxed 3 days and evapd., and the brown residue (0.8 g.) recrystd. from 20 cc. EtOH gave 0.4 g. unchanged V, m. 186-8°.  V (2.0 g.) and 4.0 g. VI in 100 cc. MeOH refluxed 1 hr. gave 1.5 g. 2,5-dimethoxyquinone, converted to 2,5-dimethoxyhydroquinone diacetate (VII).  Finely powd., crude III acetylated reductively at 90° gave VII, m. 186-8° (from Ac2O, MeOH, and iso-PrOH).  Finely powd. IIIa (5.5 g.) heated 0.5 hr. with 30 cc. 96% H2SO4 in 120 cc. H2O at 50-5° and extd. continuously with Et2O, and the ext. worked up gave 1.4 g. 2,5-dihydroxy-1,4-benzoquinone(VIII), light yellow crystals which slowly became yellow-orange on standing, also obtained from IV in the same manner.  I (1.0 g.) in 80 cc. boiling 2N NaOH dild. with dioxane to soln., refluxed 1 hr., cooled, acidified, and extd. with Et2O, the ext. evapd., the residue extd. with hot C6H6, and the C6H6 evapd. gave VIII.  VIII (0.7 g.) in 50 cc. abs. EtOH treated with 1 cc. Et2O-BF3, allowed to stand 5 hrs., distd. to beginning crystn., and cooled to room temp. gave 0.3 g. V, m. 188-9°.  VIII (1.4 g.) treated 5 min. with 20 cc. Ac2O and 3 cc. Et2O-BF3 and poured into H2O gave 1.0 g. 2,5-diacetoxy-1,4-benzoquinone, canary-yellow plates, m. 150-5° (decompn.), which was converted by reductive acetylation to 1,2,4,5-tetraacetoxybenzene (IX).  VIII (1.4 g.), 30 cc. Ac2O, and 15 cc. Et3N subjected to a reductive acetylation and cooled to -20° gave 1.0 g. IX, m. 228-30°, which deacetylated with HCl in MeOH and methylated with Me2SO4 yielded 1,2,4,5-tetramethoxybenzene, m. 101-2°.  Cu(OAc)2 (10 g.), 21.3 g. piperidine, and 150 cc. MeOH treated with 7.9 g. 1,4-naphthoquinone in 400 cc. MeOH, the MeOH evapd., the residue treated with 8 cc. 96% H2SO4 in 250 cc. H2O, and the product recrystd. from iso.ovrddot.octane and then from 25 cc. MeOH gave 10.5 g. 2-(1-piperidyl)-1,4-naphthoquinone, m. 94-6° (from iso.ovrddot.octane), which subjected to a reductive acetylation yielded 78% 2-(1-piperidyl)-1,4-naphthoquinone diacetate, m. 130-1° (from EtOAc).



Derivatives of pentahydroxybenzene and a synthesis of pedicellin.    
Baker, Wilson.   
J. Chem. Soc.  (1941)
Abstract
The derivs. of C6H(OH)5 which have been isolated from plant sources are listed and 4 methods of synthesis are reviewed.  1,2,3-C6H3(OH)3 (126 g.), methylated at 18-22°, gives 155 g. of the tri-Me ether; oxidation with HNO3 in EtOH at 50° gives 124 g. of 2,6-(MeO)2C6H2O2; reduction with Na2S2O4 gives 110 g. of the quinol which with Me2SO4 and NaOH in EtOH yields 54 g. of crude 1,2,3,5-C6H2(OMe)4 (I).  Addn. of 50 g. of I to 50 g. AlCl3 in 250 cc. ether with cooling, followed by 25 g. AcCl during 1 hr. with cooling and stirring for a further 6 hrs., gives 70% of 2,3,4,6-HO(MeO)3C6HAc (II), m. 103-5°; oxidation of 22.6 g. of II with 142 cc. 3% H2O2 in dil. NaOH at 20° gives 12.3 g. of 1,2-dihydroxy-3,4,6-trimethoxybenzene (III), m. 82° (di-Ac deriv., m. 147°).  Methylation of 10 g. of III gives about 10 g. of C6H(OMe)5 (IV), b14 150°, b21 167°, m. 58-9°.  Gallacetophenone (67.2 g.) with Me2SO4 and K2CO3 in C6H6, refluxed 6 hrs., gives 51 g. of 2,3,4-HO(MeO)2C6H2Ac (V), m. 77°, and about 10 g. of the tri-Me ether, b20 178°; oxidation of 20.2 g. of V with K2S2O8 in aq. NaOH gives 6.6 g. of 2,5,3,4-(HO)2(MeO)2C6HAc (VI), m. 119°.  VI (21.2 g.) yields with Me2SO4 and K2CO3 in C6H6 (refluxing 14 hrs.) 16.5 g. of 2-hydroxy-3,4,5-trimethoxyacetophenone (VII), pale yellow, m. 86°; Cu(OAc)2 in dil. EtOH gives a green co.ovrddot.ordinated Cu deriv.; NaOH gives a bright yellow soln. and alc. FeCl3 gives a deep slate-blue color.  Oxidation of 11.3 g. of VII with alk. H2O2 yields 7.8 g. of 1,2-dihydroxy-3,4,5-trimethylbenzene (VIII), m. 90-1°; dil. NaOH gives a light green soln. turning to yellow; aq. FeCl3 yields an orange color turning to cherry-red; excess FeCl3 gives a deep brown soln.; di-Ac deriv., m. 77°.  VIII with Me2SO4 yields V.  2,5,4,6-(HO)2(MeO)2C6HAc (8 g.), Me2SO4 and K2CO3 in C6H6, refluxed 14 hrs., give 1.3 g. of 2-hydroxy-4,5,6-trimethoxyacetophenone, bright yellow oil, b27 184-6°; the Cu deriv. is green; FeCl3 yields a deep violet-gray color; oxidation with alk. H2O2 gives VIII.  III (1 g.) in 20 cc. H2O, treated dropwise at 10° with 2 g. FeCl3 in 10 cc. H2O, gives after 4 hrs. 0.65 g. of 2-hydroxy-3,6-dimethoxy-1,4-benzoquinone (IX), dark red, m. about 208°; from AcOH it seps. as scarlet plates which appear to contain solvent of crystn.; in dil. NaOH IX gives an intensely purple-red soln. from which it is pptd. unchanged by acid.  IX and Ac2O with a little H2SO4 give the 2-Ac deriv. (X), bright yellow, m. 147°; this also results on boiling with Ac2O or with Ac2O and C5H5N at 40° or at room temp.  Reduction of X with Na2S2O4 in dil. EtOH at 60° gives 2-acetoxy-3,6-dimethoxyquinol, m. 151°; methylation gives IV; boiling Ac2O gives the diacetate, m. 114-15°.  Reduction of IX yields 2-hydroxy-3,6-dimethoxyquinol, m. 144°; FeCl3 gives a red soln. which, if in sufficient concn., deposits IX.  II. (11.2 g.) and K2S2O8 in dil. alkali, followed by hydrolysis, give 3.5 g. of 2,5-dihydroxy-3,4,6-trimethoxyacetophenone, yellow, m. 116-17°; FeCl3 in EtOH gives an apple-green color; methylation of 5.5 g. gives 4.8 g. of 2,3,4,5,6-pentamethoxyacetophenone (XI), b13 163°, m. 43°.  XI (0.7 g.), 0.14 g. Na and 2.1 g. BzOEt, heated 1.5 hrs. at 125°, give 0.08 g. of 2,3,4,5,6-pentamethoxydibenzoylmethane, pale yellow, m. 91°; FeCl3 gives a cherry-red color.  XI and BzH with EtONa give 2,3,4,5,6-pentamethoxyphenyl styryl ketone (pedicellin), m. 93°.  IV (5 g.) and then 5 g. AcCl, added to 5 g. AlCl3 in 25 cc. ether, give after boiling with dil. HCl 1.7 g. of 2-hydroxy-3,4,5,6-tetramethoxyacetophenone (XII), bright yellow oil, b14 183°; it is very slightly volatile with steam; aq. and alc. FeCl3 give intense brown and deep brownish-green colors, resp.; Cu gives a green co.ovrddot.ordinate Cu deriv.  Oxidation of XII with alk. H2O2 at 46° gives a crude 1,2-(HO)2C6(OMe)4 which with Me2SO4 and KOH gives C6(OMe)6, m. 81°.  In the demethylation of o-MeO ketones by AlCl3 in ether, the MeO groups must be activated by CO groups in either the o- or p-positions.  Demethylation in the p-position takes place much less readily than in the o-position but has been observed in the case of 2,3,4-(MeO)3C6H2Ac which by the prolonged action of boiling ethereal AlCl3 yields 3,2,4-MeO(HO)2C6H2Ac.  The remarkably inert nucleus of 1,2,4,5-C6H2(OMe)4 is not attacked by AlCl3 and AcCl in ether.

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Fully Informed Jury!

(http://www.fija.org/)

Foxy: I have seen reaction with better rdt than those you have posted. Anyway I haven't see any reaction without DMS/CH3I/DMC.
Peyote/other italian bee: Can you traduct this, this is the ialian ref I was speaking:
"Parte sperimentale: Preparazione del para-dimetossi-benzolo dall' 1-4 benzochinone.
a) riduzione con amalgama di alluminio cd idrato di potassio. -Ad una soluzione di 5gr. di chinone in 80 cc. di alcool metilico all'80% si aggiungono a freddo 5 gr. di amalgama di alluminio preparata secondo Wislicenus (11), poi lentamente 200.gr di, una soluzione al 50% di idrato di potassio.
Si fa bollire a ricadere per un'ora, poi si aggiungono a poco a poco 30 gr. di soolfato dimetilico ed altri 35 gr. di soluzione di KOH e si continua ancora a riscaldare per un'altra ora.
La soluzione giallastra, che ha netta reazione alcanica, viene distillata in corrente di vapore; in tal modo viene trascinata la maggior parte del para-dimetossi-benzolo che si puo separare quantitativamente per estrazione con etere del distillato. Per evaporazione dell'etere si ottengono gr. 4,0 (pari all'80%) del composto fondente a 51°.
Acidificando il residuo ed estraendo con etere si ricavano 0.3 gr. dihidrochinone monometil-etere.
Per fissare queste condizioni sopno state fatte diverse prove variando le quantita di alcali di soolfato dimetilico e la concentrazio,ne della soluzione alcoolica."
After that they tried some variation on the concentration/ration of the reactant, with loss of dimethyl ether for monomethyl ether.
Now I thought that reduction of benzo in MeOH doesn't lead to dimethoxybenzene, it's only some misrepresentation in the summary of the reactions I think. Antocho prove me wrong if you want.
So we must have three steps:
1) radical alkylation of quinone
2) reductive methylation of quinone with alkylating agent and Na2S2O8 or Na2S2O4 (or alhg but it suck) (or maybe NaHSO3) This second step can be selective to the quinone
3) transformation of the propanone to the amine (or deprotection of the amine if we use the alanine)
Foxy: the method with the organoaluminium is not the same as  the radical decarboxylation. It is more tedious I think and less easy. I have seen other method like one reacting with pyridine and 2,4 dioxo pentane to form the phenylacetone, but poly alkylation occur.

To me, it seems quite obvious what the really ironically elegant and oh so nifty reaction scheme here is:

Bromination of benzoquinone with N-bromosuccinimide followed by recovery and purification of the formed succinimide and 2-bromo-1,4-benzoquinone.

Reaction of succinimide with NaOH/NaOCl to yield the gamma-aminopropanoic acid.

Reaction of the formed amino acid with the formed bromo-benzoquinone in water with AgNO₃ and ammonium peroxydisulfate to form the 2-ethylamino-5-bromo-1,4-benzoquinone.

Reduction of this compound in methanolic Al/Hg to convert the quinone into the dimethoxy derivative, lovingly known as 2C-B

                                                   PrimoPyro

---

Vivent Longtemps la Ruche!

Yeah it's fun but the problem if that the reaction is not very regioselective. One of their paper say that 2-methoxy-1,4 quinone is alkylated para to the methoxy (don't remember the %, I'll tell you latter) and that the methoxy is more directive than the methyl (toluquinone, more or less 35% para and 30% ortho). I don't know if the bromo counterpart will orient para, it is not in their article, I'll read it more carefully. Instead of the reduction with Al/Hg I prefer  the use of the same peroxydisulfate for this purpose and CH3I. I think after my research that it does not work without an alkylating agent, they use Al/Hg with DMS. It's simpler to stay with the peroxydisulfate reduction. And I think there can be side reaction with the not protected amine and the not methylated quinone.
I think that I'll stock up the succinimide from my previous bromination, convert it with NaOH/NaOCl, protect it with acetyl chloride, alkylate quinone with peroxydisulfate/AgNO3, reduce quinone with peroxydisulfate/CH3I, convert the amide to the amine with Zn, react the 2CH with NBS to give 2CB and purify the succinimide for the next run.

Pyro
Is there a reference for the Al/Hg in methanol to get the dimethoxy?

 
Synthesis of 2-bromo-1,4-benzoquinone

From the KBrO3 oxidation of commercially available bromo hydroquinone according to McElvain, S. M.; Engelhardt, E. L. J. Am. Chem. Soc. 1944, 66, 1077-1080.

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Fully Informed Jury!

(http://www.fija.org/)

Poix - A writeup of such a novel working synthesis would get the Rhodium award 2002 for the most ingenious phenethylamine synth.

Hello all
Can some bee get me this ref: Synth commun 2001 31(10) 1467-1475 : It describe the synthesis of some substitued gbl with oxidative decarboxilation of acids, they speak of 1,4 dmb too. They use Ag and peroxydisulfate but also Mn and Ce or Pb. I would like to know what they say about ox. decarb. with silver and the others element. If I can get the experimental section with Ag it would be cool too.

In fact I'm trying to reduce the use of AgNO3 because it's somewhat expensive. This ref: J am chem soc 1970 1651-59 it's a review of the role of silver in this reaction. They say 'the presence of 0.01M silver nitrate markedly catalyzed the decarboxylation (t1/2=11min). The half-life of the peroxydisulfate in the presence of 0.01M AgNO3 was 11min, whereas it was 600min in the absence of silver(I).' With AgNO3 0.005M the decarboxylation is more than two fold slowed. In the reaction from orgsyn, they use ~.036 M Ag.
Some equation:
 .006 in 166ml-> 0.036 M Ag
   0.01M Ag is OK -> we can dilute it 3 times
 quinone MM 108, 5.4g -> 0,15 mol 16,2g
RDT 50% -> 2C-H MM 181 -> 0.15 * 90 = 13.5g
for 13.5g we use 1g of AgNO3, 25g is 45$ -> ~2$
for 50g ~8$
If the reaction work with .01M AgNO3, and if the Rdt is ~50% (it may be a little less) it will cost ~8$ of Ag for 50g 2C-H. It is reasonable I think. But if we can use Ce or recyclate Ag or maybe if we can reuse the aqueous medium more than once it will cost less.

Primo: from Acta chem Scand 27(1973) No. 9 p 3212:
Isopropylation of toluquinone: isomer ratio:
m: 25% p: 40% o: 35%
Pentylation of 2-methoxy-1,4-benzoquinone:
m: 5% p: 68% o: 27%
'In view of the nucleophilic character of the alkyl radical this distribution pattern is expected.'
pentylation of 2-meo-1,4-benzoquinone:
products:
3-pentyl yield 2%
5-pentyl 34%
6-pentyl 13%
3,5 dipentyl 1%
3,6 dipentyl 1%
5,5 dipentyl 2%

I think that this reaction is good with simetrical quinone like benzoquinone, but not so good with unsimetrical quinone like bromoquinone.

Question: what pattern of substitution could be expected with bromoquinone and CF3-quinone? Anyone? Para? Meta?

If someone can verify the reaction from pyro with succinimide to alanine it would be cool too. Anyone wish to try it?

Aloha P iX

But that quinones can be trifluoromethylated and methanolyzed to 2,5-dimethoxy-trifluoromethylbenzene in one pot this cheap is very cool. From there it is the three usual common steps to create 2C-TFM, either via the aldehyde or via the acetonitrile.

I've got a verification of the succinimide to B-alanine route from Merck index. It's in org synthesis: succinimide + KOBr + 2 KOH -> B-alanine +KBr +K2CO3. Bleach and NaOH could be substitued. From the same number of org. synth. there is a preparation of succinimide from distillation of succinic acid/ammonia.

So there is no problem to obtain the B-alanine. We can also obtain it from methyl acrylate with aqueous ammonia or ethyl acrylate with alcoholic ammonia. Any OTC use for methyl acrylate?

The cool thing with this synthesis is the OTCness of all it's reagents (except MeI). Do you know that MeI/MeBr are used as soil fumigant? Maybe OTCness here? Otherwise MeI can be made from aq KI with H2SO4/MeOH in 90% yield (Czech patent) or from iodine in AcOMe with Al and AcOH (65% calculated on Iodine).

On my page there are OTC MeI, Me2SO4 and NaMeSO4 references to be found. All works as alkylating agents. But you would have to use special reaction conditions if you want to use the CH3X for N-methylating an amino acid (also featured on my page, but illustrated for amphetamines).